Intracranial Genetically Modified Immune Cells (TGFβR2KO/IL13Rα2 CAR T-Cells) for the Treatment of Recurrent or Progressive Glioblastoma or Grade 3 or 4 IDH-Mutant Astrocytoma

PRIMARY OBJECTIVE: I. Assess the safety and determine the maximum tolerated dose (MTD) of intracranial (IC) administration of TGFβR2KO/IL13Rα2-CAR T cell therapy. SECONDARY OBJECTIVES: I. In participants who receive at least 50% of the assigned cell dose for each of the four cycles and at least 70% of the total cumulative dose for all cycles (1-4): Ia. Estimate overall response rates (ORR) and complete response (CR) rate at 3, 6, 9-months; and Ib. Estimate overall survival (OS) at 9-months. II. Determine feasibility of IC administered TGFβR2KO/IL13Rα2-CAR T cell therapy as assessed by leukapheresis and manufacturing processes, including ability to meet the TGFβR2KO/IL13Rα2-CAR T cell dose and product release requirements; III. Determine the maximum feasible dose (MFD), as assessed by leukapheresis, manufacturing, toxicity, and response data. EXPLORATORY OBJECTIVES: I. Descriptively compare CAR T persistence in the cerebrospinal fluid (CSF) and the blood, cytokine dynamics, and response among patients treated on institutional review boards (IRBs) 24717 and 13384. II. Profile cytokine levels and graphically evaluate cytokine levels over time and changes in the presence of cytokine release syndrome (CRS) toxicity (CSF, tumor cavity fluid \[TCF\], peripheral blood \[PB\]). III. Describe CAR T cell and endogenous immune cell populations (CSF, TCF, PB). IV. Describe tumor and tumor micro-environment markers and their relationship to treatment outcomes. V. For participants who undergo secondary resection(s) or autopsy on study: Va. Evaluate CAR T cell persistence in the tumor micro-environment, location of the CAR T cells with respect to the injection site; and Vb. Evaluate changes in IL13Rα2 antigen expression levels pre and post CAR T cell therapy. VI. Through the use of biomathematical modeling techniques, characterize tumor growth and its relationship to treatment outcomes. OUTLINE: This is a dose-escalation study. Patients undergo leukapheresis and standard of care surgical resection with or without placement of Rickham catheter. Starting on day 0, patients receive autologous TGFβR2KO/IL13Rα2-CAR T cells intracranially over approximately 5 minutes once weekly (QW). Cycles repeat weekly for up to 4 cycles (28 days) in the absence of disease progression or unacceptable toxicity. Patients may receive additional cycles if they continue to meet infusion criteria and have doses available for infusion. Patients also undergo CSF and blood sample collection and fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) and MRI throughout the study. Additionally, patients may undergo echocardiography at screening. After completion of study treatment, patients are followed up on day 30, months 3, 6, 9 and 12, then yearly for up to 15 years.